Hormonal Control of Bone Architecture Throughout the Lifespan: Implications for Fracture Prediction and Prevention.

BACKGROUND: Skeletal modeling in childhood and adolescence and continuous remodeling throughout the lifespan are designed to adapt to a changing environment and resist external forces and fractures. The flux of sex steroids in men and women, beginning from fetal development and evolving through infancy, childhood, puberty, young adulthood, peri/menopause transition, and postmenopause, is critical for bone size, peak bone mass, and fracture resistance. OBJECTIVE: This review will highlight how changes in sex steroids throughout the lifespan affect bone cells and the consequence of these changes on bone architecture and strength. METHODS: Literature review and discussion. RESULTS: The contributions of estrogen and testosterone on skeletal development have been difficult to study due to the reciprocal and intertwining contributions of one on the other. Although orchiectomy in men renders circulating testosterone absent, circulating estrogen also declines due to testosterone being the substrate for estradiol. The discovery of men with absent estradiol or resistance to estrogen and the study of mouse models led to the understanding that estrogen has a larger direct role in skeletal development and maintenance in men and women. The mechanistic reason for larger bone size in men is incompletely understood but related to indirect effects of testosterone on the skeleton, such as higher muscle mass leading to larger mechanical loading. Declines in sex steroids during menopause in women and androgen deprivation therapies in men have profound and negative effects on the skeleton. Therapies to prevent such bone loss are available, but how such therapies can be tailored based on bone size and architecture remains an area of investigation. CONCLUSION: In this review, the elegant interplay and contribution of sex steroids on bone architecture in men and women throughout the lifespan is described.

Rates of Pheochromocytoma/Paraganglioma Screening in At-Risk Populations.

CONTEXT: Pheochromocytomas and paragangliomas (PPGL) are rare causes of secondary hypertension, but when unrecognized, they can lead to serious complications. Data regarding PPGL screening are lacking. OBJECTIVE: This study aimed to assess the rates and patterns of PPGL screening among eligible patients. METHODS: We conducted a retrospective review of adults with hypertension seen in outpatient clinics of a large academic center between January 1, 2017, and June 30, 2020. We included patients with treatment-resistant hypertension, hypertension at age < 35 years, and/or adrenal mass(es). RESULTS: Of 203 535 patients with hypertension identified, 71 088 (35%) met ≥ 1 inclusion criteria, and 2013 (2.83%) were screened for PPGL. Patients screened were younger (56.2 ± 17.4 vs 64.0 ± 17.1 years), more often women (54.1% vs 44.2%), and never-smokers (54.6% vs 47.5%, P < 0.001 for all). The rate of screening was highest in patients with hypertension and adrenal mass(es) (51.7%, vs 3.9% in patients with early-onset hypertension, and 2.4% in those with treatment-resistant hypertension). Multivariable logistic regression showed higher odds ratio (OR) of PPGL screening in women (OR [95% CI]: 1.48 [1.34-1.63]); Black vs White patients (1.35 [1.19-1.53]); patients with adrenal mass(es) (55.1 [44.53-68.15]), stroke (1.34 [1.16-1.54]), dyslipidemia (1.41 [1.26-1.58]), chronic kidney disease (1.40 [1.26-1.56]), and obstructive sleep apnea (1.96 [1.76-2.19]). CONCLUSION: PPGL screening is pursued in roughly half of patients with adrenal nodules and hypertension, but rarely in patients with treatment-resistant or early-onset hypertension. Similar to screening for other forms of secondary hypertension, PPGL screening occurs more often after serious complications develop.

Primary Aldosteronism Screening Rates Differ with Sex, Race, and Comorbidities.

Background Primary aldosteronism (PA) is a common but under-recognized cause of secondary hypertension. Data directly comparing screening rates across single and overlapping indications are lacking. Methods and Results We conducted a retrospective review of adults with hypertension seen in outpatient clinics at a tertiary referral academic center between January 1, 2017, and June 30, 2020. We included patients with hypertension plus at least one of the following: resistant hypertension; age<35 years; obstructive sleep apnea; hypokalemia; or an adrenal mass. We excluded patients with adrenal insufficiency, severe renal disease, or heart failure, and renovascular hypertension. Of 203 535 patients with hypertension, 86044 (42.3%) met at least 1 PA screening criterion, and of these, 2898 (3.4%) were screened for PA. Screening occurred in 2.7% of patients with resistant hypertension; 4.2% of those with obstructive sleep apnea; 5.1% of those <35 years; 10.0% of those with hypokalemia; and 47.3% of patients with an adrenal mass. Screening rates were higher in patients with multiple risk factors: 16.8% for ≥3, 5.7% for 2, and 2.5% for 1 criterion. Multiple logistic regression showed that the odds of PA screening were higher in patients with hypokalemia: odds ratio (95% CI): 3.0 (2.7-3.3); women: 1.3 (1.2-1.4); Black versus White: 1.5 (1.4-1.7); those with obstructive sleep apnea, chronic renal disease, stroke, and dyslipidemia. Conclusions Consideration for PA is given in a small subset of at-risk patients, and typically after comorbidities have developed.

Functional imaging in ectopic Cushing syndrome.

PURPOSE OF REVIEW: Ectopic adrenocorticotropic hormone (ACTH)-secreting tumors are commonly small, yet they often lead to fulminant forms of Cushing syndrome. High-resolution functional imaging modalities, such as [Ga]-DOTATATE, have been recently introduced in clinical practice for the identification of neuroendocrine tumors. In this review, we focus on the performance of [Ga]-DOTATATE as a tool for localizing primary and metastatic sources of ectopic Cushing syndrome (ECS). RECENT FINDINGS: Prompt surgical removal of ectopic ACTH-secreting tumors is the mainstay of therapy in patients with ECS. Detecting such tumors with conventional cross-sectional imaging is often unsuccessful, owing to their small size. [Ga]-DOTATATE has been approved in 2016 by the Federal Drug Administration for imaging well differentiated neuroendocrine tumors. Data regarding the performance of [Ga]-DOTATATE for detecting ectopic ACTH-secreting tumors remain limited, in part owing to the recent introduction of this imaging modality in clinical practice, and in part because of the low prevalence of ECS. Nevertheless, [Ga]-DOTATATE has been reported to be useful in identifying primary and metastatic ectopic ACTH-secreting lesions that were not apparent on other imaging studies, impacting the clinical care of many patients with ECS. SUMMARY: [Ga]-DOTATATE-based imaging, which targets the somatostatin receptors abundantly expressed in neuroendocrine tumors, has generally high, although variable resolution in detecting the source(s) of ECS.